Apparatus and method for detecting disconnection of an intravascular access device

ABSTRACT

An apparatus and method are disclosed for detecting the disconnection of a vascular access device such as a needle, cannula or catheter from a blood vessel or vascular graft segment. A pair of electrodes is placed in direct contact with fluid or blood in fluid communication with the vascular segment. In one embodiment, the electrodes are incorporated into a pair of connectors connecting arterial and venous catheters to arterial and venous tubes leading to and from an extracorporeal blood flow apparatus. Wires leading from the electrodes to a detecting circuit can be incorporated into a pair of double lumen arterial and venous tubes connecting the blood flow apparatus to the blood vessel or vascular graft. The detecting circuit is configured to provide a low-voltage alternating current signal to the electrodes to measure the electrical resistance between the electrodes, minimizing both the duration and amount of current being delivered. Detection of an increase in electrical resistance between the electrodes exceeding a pre-determined threshold value may be used to indicate a possible disconnection of the vascular access device.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a Non-provisional Application which claimspriority from U.S. Provisional Patent Application Ser. No. 61/256,735,filed Oct. 30, 2009 and entitled Device and Method for DetectingDisconnection of an Intravascular Access Device, which is incorporatedherein by reference in its entirety.

BACKGROUND

The present invention relates generally to systems and methods to detectdisconnection of an indwelling vascular line, such as a catheter orneedle, or its attached tubing. If not quickly detected, a disconnectioncan lead to rapid exsanguination, particularly when the blood in thecatheter or tubing is under positive pressure. Examples of circumstancesinvolving positive intravascular pressure include the positive pressureassociated with an artery or arterio-venous fistula, or the positivepressure associated with an extracorporeal blood pump circuit. Inhemodialysis, for example, a blood pump can generate blood flow rates of400-500 ml/min, making rapid, reliable disconnect detection particularlydesirable. Indeed any medical treatment involving relatively high flowor high pressure extracorporeal circulation (such as, for example,hemoperfusion or cardiopulmonary bypass) can be made safer by having aneffective system to monitor the integrity of the arterial (withdrawal)and venous (return) blood lines.

In hemodialysis, for example, extracorporeal blood circulation can beaccomplished with vascular access using either a single indwellingcatheter, or two separate indwelling catheters. In a single cathetersystem, blood is alternately withdrawn from and returned to the body viathe same cannula. A disconnection in this system can be quickly detectedby placing an air monitor in the line at or near the pump inlet, becauseair will be drawn into the line from the disconnection site during theblood withdrawal phase of the pumping. On the other hand, in atwo-catheter system, blood is typically continuously withdrawn from thebody via one catheter inserted in a blood vessel or fistula, andreturned to the body via the second catheter inserted in the same vesselsome distance from the first catheter, or in a separate blood vesselaltogether. In the two-catheter system, it is also possible to monitorfor catheter or tubing dislodgement in the blood withdrawal or‘arterial’ segment by using a sensor to detect the presence of air beingentrained into the arterial tubing as blood is withdrawn from the bloodvessel under negative pump pressure and/or positive fistula pressure.However, air-in-line detection cannot reliably detect a disconnection ofthe venous (return) segment of the extracorporeal circuit. In this case,if the blood-withdrawal path remains intact, air will not be introducedinto the line. Thus it is particularly important to be able to detect adisruption in the continuity of the return line from the extracorporealpump to the vascular access site.

Attempts have been made to develop systems to detect dislodgment basedon the electrical, mechanical or acoustical properties of blood in theextracorporeal circuit. These systems have not been very effectivebecause of the relatively high impedance of a blood circuit thatincludes long stretches of tubing, one or more blood pumps, valves, airtraps and the like. Furthermore, the electrical interference generatedby various devices along the blood path may obscure the signal that oneis attempting to monitor.

An electrical signal can be introduced into the blood circuit throughinduction using a field coil surrounding a section of the blood tubing.It may also be introduced through capacitive coupling. For reasons ofpatient safety, the strength of an electrical signal introduced into theblood circuit necessarily must be small. However, the dielectricproperties of the wall of the blood tubing can cause excessive noise orinterference when attempting to detect conductivity changes in the bloodfrom an electrical signal introduced through inductive or capacitivecoupling. Therefore, it may be more desirable to introduce a brief,small electrical signal through direct contact with the blood path, tolimit the length (and therefore impedance) of the blood path beingmonitored, and to perform the monitoring function at a suitable distancefrom any interference-producing components.

SUMMARY

In one aspect, the invention comprises a system for detecting whether avascular access device, such as a needle, cannula, catheter, etc.becomes disconnected or dislodged from a blood vessel or vascular graft.The system includes a fluid delivery device that provides for the flowof a liquid through a tube or conduit into the blood vessel via anindwelling needle or catheter at a first site on the blood vessel orgraft. The fluid may be an electrolyte solution or other solutionsuitable for intravenous infusion, or it may be blood or bloodcomponents. An electrode is disposed to be in contact or fluidcommunication with the lumen of the conduit, and a second electrode isdisposed to be in fluid communication with blood within the blood vesselor graft via a second on the blood vessel or graft. An electroniccircuit is connected to the first and second electrodes, and configuredto deliver a control signal to the first and second electrodes in orderto measure the electrical resistance of the fluid between the first andsecond electrodes, such that at least one of the electrodes is locatedcloser to the blood vessel or graft than to the fluid delivery device.In some embodiments the electrode is located at about 50-70% of thedistance from the fluid delivery device to the blood vessel or graft. Inother embodiments, the electrode is located at about 70-90% or more ofthe distance from the fluid delivery device to the blood vessel orgraft. The fluid delivery device can include a pump, either for blood orfor other therapeutic or diagnostic fluid. The fluid delivery device canbe part of a hemodialysis blood flow circuit, which may or may notinclude a blood pump, a dialyzer cartridge, or an air trap andassociated tubing. The second electrode may be placed in contact withthe lumen of a second conduit or tube that is in fluid communicationwith the blood vessel or graft at the second site. The second conduitmay form part of a fluid flow path from the blood vessel or graft to thefluid delivery device. The fluid in the second conduit may be bloodbeing delivered to an extracorporeal blood flow circuit.

The system may comprise a first and second connector connecting a pairof vascular access catheters accessing a blood vessel segment orvascular graft segment at two different sites. The first and secondconnectors may each connect to a flexible tube leading to the fluiddelivery device. Each connector may include an electrode that is exposedto the lumen of the connector. A wire may be attached to each connector,the wire being connectable on its other end to the electronic circuit.The flexible tubes may be double lumen tubes having a first lumen forcarrying fluid and a second lumen for carrying a wire. The wires of eachtube may be connected on the other end of the tube to a connector forconnection to the electronic circuit.

The electronic circuit or an associated microprocessor may be configuredto convert the voltages measured across terminals connected to theelectrodes by the electronic circuit into resistance values. The systemmay comprise a controller configured to receive a signal from theelectronic circuit or microprocessor, the signal representing theelectrical resistance between the electrodes, the controller beingprogrammed to trigger an alert signal when the electrical resistancevalue exceeds a pre-determined threshold. The alert signal may be anaudible or visual signal to the person whose blood vessel is beingaccessed, and optionally an alert signal may include an electricalcommand to a tubing occluder apparatus. The tubing occluder apparatusmay be actuated to mechanically occlude one or more of the tubes leadingfrom the vascular access sites. The tubing occluder may operate in anumber of ways, such as, for example electromechanically, hydraulically,or pneumatically.

In another aspect, the invention comprises an apparatus for monitoringthe continuity between a vascular access device and a blood vessel orvascular graft segment, comprising, a first and second vascularconnector, the first connector being attached on a proximal end to adistal end of a fluid-carrying lumen of a first double-lumen tube, andthe second connector being attached on a proximal end to a distal end ofa fluid-carrying lumen of a second double-lumen tube. The firstconnector comprises a first electrode in contact with a lumen of thefirst connector and electrically connected to a wire within awire-carrying lumen of the first double-lumen tube, and the secondconnector comprises a second electrode in contact with a lumen of thesecond connector and electrically connected to a wire within awire-carrying lumen of the second double-lumen tube. The wire within thefirst double-lumen tube and the wire within the second double-lumen tubeare each connected to an electrical connector at a proximal end of thedouble-lumen tubes. The distal end of each connector may be configuredwith a locking feature to provide a reversible, air-tight connectionbetween the connector and a mating connector of a vascular catheter. Theproximal end of the double-lumen tubes can be connected to a blood pumpon an arterial side, and an air trap on a venous side; and in ahemodialysis system, the blood pump and air trap may each be reversiblyconnectable to a dialyzer cartridge.

In another aspect, the invention comprises a vascular connectorcomprising a proximal fluid connection end, a distal fluid connectionend, and an electrode configured to electrically connect afluid-carrying lumen of the connector with a wire external to thevascular connector. The proximal end of the connector may be configuredto connect with a flexible tube, and the distal end of the connector maybe configured to connect with a mating connector of a vascular catheter.The electrode may be installed in a conduit on the connector thatconnects the lumen of the connector to the exterior of the connector.The electrode may be lodged into the conduit in a manner to provide anair-tight seal between the lumen and the exterior of the connector. Anelastomeric member such as an O-ring may be installed between theelectrode and the conduit to contribute to the air-tight seal.

In another aspect, the invention comprises an electrical circuit formeasuring the resistance of a liquid between a first and secondelectrode, the first electrode connected to a first terminal of theelectrical circuit, and the second electrode connected to a secondterminal of the electrical circuit, comprising a capacitor C1 connectedon a first end to the first terminal and a capacitor C2 connected on afirst end to the second terminal; a known reference resistance Rrefconnected on a first end to a second end of capacitor C1; switchingmeans for connecting either (a) a first reference voltage V+ to a secondend of Rref, and a lower second reference voltage V− to a second end ofC2 to form a first switch configuration or; (b) the first referencevoltage V+ to the second end of C2 and the lower second referencevoltage V− to the second end of Rref to form a second switchconfiguration; and measuring means for measuring a voltage Vsense at theconnection between C1 and Rref; such that the electrical circuit isconfigured to determine the value of the resistance of the liquid basedon the known reference resistance Rref and the observed voltage Vsensefor each of the first and second switch configurations. The resistanceRref may be chosen to be a value that permits conductivity measurementof an electrolyte solution or other solution suitable for intravenousinfusion. The electrolyte solution may include dialysate solution. Theresistance Rref may also be chosen to permit measurement of theresistance of a volume of blood between the first and second electrodes.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic representation of a conductivity circuit in anillustrative embodiment;

FIG. 2 is a diagram of the electrical waveforms processed by the circuitof FIG. 1;

FIG. 3 is a representative graph of the noise/error sensitivity of thecircuit of FIG. 1 plotted against the ratio of unknown/referenceresistance in the circuit;

FIG. 4 is a schematic representation of an exemplary blood flow circuitof a hemodialysis system;

FIG. 5A is a side view of a connector that may be used in the blood flowcircuit of FIG. 4;

FIG. 5B is a cross-sectional view of the connector of FIG. 5A;

FIG. 6 is a cross-sectional view of the connector of FIGS. 5A and 5B,with an attached wire and flexible tubing;

FIG. 7A is a perspective view of an alternate embodiment of a connectorthat may be used in the blood flow circuit of FIG. 4;

FIG. 7B is a top view of the connector of FIG. 7A;

FIG. 7C is a cross-sectional view of the connector of FIG. 7B;

FIGS. 8A-D are various cross-sectional views of a flexible tubeincorporating a conductive wire;

FIG. 9 is a perspective view of a flexible double-lumen tube having afluid-carrying lumen and a wire-carrying lumen;

FIG. 10 is a cross-sectional view of a connector similar to theconnector of FIGS. 7A-C, with an attached wire and tubing;

FIG. 11 is a plan view of an extracorporeal blood flow circuit used in arepresentative hemodialysis system;

FIG. 12 is a perspective view of a hemodialysis apparatus configured toreceive and operate the extracorporeal blood flow circuit of FIG. 11;

FIG. 13 is a representative plot of the resistance measured by theconductivity circuit of FIG. 1 under various conditions.

DETAILED DESCRIPTION Conductivity Circuit

An exemplary electrical circuit shown in FIG. 1 can be used to measurethe electrical conductivity or resistance of a subject fluid. In oneembodiment, the fluid may be an electrolyte solution or dialysate fluid,and the circuit may ultimately provide a measurement of the conductivityof the fluid to ensure its compatibility for intravascularadministration. In addition to monitoring the concentration of dissolvedsolutes in the fluid, the electrical circuit can also monitor for anyinterruption in the continuity of the fluid between the electrodesconnected to the circuit. For example, it can be used to monitor anintravenous fluid line for the presence of air bubbles, or for thepresence of a contaminating substance. In another embodiment, the fluidmay be blood, and a change in the measured electrical resistance of ablood flow path (for example, in a conduit) may be used to indicate if adiscontinuity occurs between the blood flow path and measuringelectrodes. For example, the blood flow path may comprise a column ofblood between two electrodes that includes indwelling needles orcatheters in a segment of a blood vessel, arterio-venous fistula orgraft. Vascular access disconnection can result in the introduction ofair into the blood flow path, causing a change in the resistivity of theblood column between the electrodes. The electrical circuit can bereadily modified (depending on its application) to adjust for thedifference between the impedance of a blood flow path and that ofdialysate fluid.

The circuit shown in FIG. 1 may be used to measure an unknown resistanceR_(x) of a subject media 1 using inexpensive electronic components,particularly where the unknown resistance involves a conductive paththrough an electrolytic fluid. A switching network 2 comprising a pairof multiplexers allows the connection of nodes V_(A) and V_(B) toreference voltages V+ and V−. The subject media 1 having unknownresistance R_(x) is connected to terminals V_(TA) and V_(TB) 3, andforms a voltage divider with reference resistor R_(ref) 4. To make aconductivity measurement, alternating voltages can be presented to thesubject media 1 via switching network 2 to the voltage divider createdby the known reference resistor R_(Ref) 4 (680Ω, for example, in thecase of dialysate fluid) and the unknown resistance R_(X) of the subjectmedia 1. The midpoint of the voltage divider 5 is measured. The signalV_(Sense) at point 5 is buffered by amplifier 10 to make the inputsignal V_(in) of the analog-to-digital converter (ADC) 11. V_(Sense)switches between two values as the voltage divider is driven first oneway and then the other way. This signal is valid only for a short periodof time after switching because the fluid in the conductivity cell 1 isAC coupled into the circuit through capacitors C1 and C2 6. ThusDC-blocking capacitors C1 and C2 6 may be used to prevent DC currentsfrom passing through the unknown resistance (which may include aconductive path through electrolytic fluid or blood). In an embodiment,series capacitors C can each comprise two capacitors in parallel, onehaving a value, e.g., of 0.1 uF, and the other having a value, e.g., of10 uF. Series resistors 7 may be used to reduce exposure by the switchnetwork and other sense circuitry to noise and surge voltages. ADC 11can take multiple samples of the signal as the circuit is switchedbetween the two configurations.

The switching network 2 can be driven by a pair of alternating binarycontrol signals 13, 14 that connect V_(A) to V+ and V_(B) to V− duringone half-cycle, and V₁₁ to V+ and V_(A) to V− during the otherhalf-cycle. This results in a waveform at the V_(sense) node 5 that issimilar to the waveform 20 shown in FIG. 2. In this embodiment, V_(Ref)is 4 volts, resulting in a V_(sense) amplitude of less than 4 volts, asshown in FIG. 2. A voltage divider 8 creates the voltages V+ and V− thatare near the positive reference voltage V_(Ref) and near ground,respectively. In one embodiment, R1 can have a value of 10 ohms, and R2can have a value of 2K ohms When both multiplexers of switching network2 are commanded to zero, the circuit is at rest and the lower voltage ispresented to terminals V_(TA) and V_(TB) 3. When V_(A) is high and V_(B)is low, the higher voltage is presented to the reference resistorR_(Ref) 4 and the lower voltage is presented to the subject media 1having unknown resistance R_(x). When V_(B) is high and V_(A) is low,the higher voltage is presented to the subject media 1 having unknownresistance R_(x) and the lower voltage is presented to the referenceresistor R_(Ref) 4.

A change in voltage ΔV_(sense) before and after each square wave edge,can be shown to depend only on the reference resistance R_(ref) 4, theunknown resistance R_(x) of subject media 1, and any series resistance(including, e.g., R_(s) 7), and is generally independent of seriescapacitance C1 or C2 6, since during this short time period thecapacitor acts as an incremental short circuit. In particular,

Δα=ΔV _(sense)/(V ₊ −V ⁻)=(R _(y) −R _(ref) −R _(th))/(R _(y) +R _(ref)+R _(th))=(ρ−1)/(ρ+1)

where R_(y)=R_(x)+2R_(s)+R_(th), where R_(th)=source series resistancefrom multiplexer 2 and voltage divider 8, and ρ=R_(y)/(R_(Ref)+R_(th)).(Source series resistance R_(th), can be derived as the sum of theresistance of multiplexer 2 and the Thevenin equivalent resistance ofthe voltage divider 8. For example, for R1=10 ohms, R2=2K ohms, thenR_(th)=R1∥(R1+R2)=9.95 ohms). Thus, if R_(y) is a short circuit, thenρ=0 and Δα=−1. The sense node's change in voltage ΔV_(sense) is thenequal to the voltage change at V_(B) which has an amplitude opposite tothe drive node at V_(A). If R_(y) is an open circuit, then ρ=∞ and Δα=1.The sense node's change in voltage ΔV_(sense) is then equal to thevoltage change at the drive node V_(A). Accordingly, if this change involtage is measured, the preceding equations can be solved for theunknown resistance R_(x):

R _(x)=ρ(R _(ref) +R _(th))−2R _(s) −R _(th), where ρ=(1+Δα)/(1−Δα)

As shown in FIG. 1, a low-pass filter 9 can be formed by resistor R_(f)and capacitor C_(f), to filter out high-frequency noise. In oneexemplary arrangement, R_(F) can have a value of 1K Ω, and C_(F) canhave a value of 0.001 uF. Buffer amplifier 10 and analog-to-digitalconverter (ADC) 11 can then measure the sensed voltage for a computer ordigital signal processor (not shown).

The reference voltages V+ and V− may be advantageously derived from avoltage divider 8 so that V+ is close to the reference voltage V_(Ref)of the ADC 11, and V− is close to the ground reference voltage of theADC 11. For example, for R₁=10Ω, R2=2 kΩ, and V_(ref)=4.0V, thenV+=3.980V, and V−=0.020V. This places both voltages within but near theedges of the active sensing region of the ADC 11, where they can be usedfor calibration (discussed below). Switch SW₁ 12 may be used to helpcalibrate the load resistance sensing.

Several improvements may decrease errors related to variations ofcomponent values. First, a calibration step can be introduced whereV_(A) is switched to V+ for a relatively long period of time, untilsettles and is approximately equal to V+, at which point ADC 11 can takea measurement of V_(sense). A second calibration step can involveswitching V_(A) to V− for a relatively long period of time, untilV_(sense) settles and is approximately equal to V−, at which point ADC11 can take another measurement of V_(sense). This allows the ADC 11 tomeasure both V+ and V−.

Secondly, as shown in FIG. 2, while the square wave is switching, ADC 11readings before and after both edges of the switching waveform may beused to compute the dimensionless quantity Δα:

Δα=ΔV _(Sense)/(V+−V−)=[(V2−V1)+(V3−V4)]/2(V+−V−)

As a result, both edges of the waveform can be used to measureΔV_(Sense)=[(V2−V1)+(V3−V4)]/2, so that asymmetric responses to thecircuit are likely to be canceled out. Alternatively, an average voltageat about the midpoint of the waveform may be used; so that, for example,Δα=ΔV_(Sense)/(V+−V−)=[(V7−V6)+(V7−V8)]/2(V+−V−), andΔV_(Sense)=[(V7−V6)+(V7−V8)]/2. In addition, only differentialmeasurements of the input signal V_(in) of the ADC 11 can be used. Thus,any offset errors of the buffer amplifier 10 and ADC 11 can be canceledout. Also, Δα is a ratiometric quantity based on measurements using thesame signal path. Thus, any gain errors of the ADC 11 can also becanceled out.

The reference resistor R_(Ref) 4 may be optimally chosen to be equal tothe geometric mean of the endpoints of the desired range of unknownresistances, taking series resistances R_(s) 7 into account. Forexample, if R_(s)=100Ω and R_(x) varies from 100Ω to 3000Ω, thenR_(y)=R_(x)+2R, varies from 300Ω to 3200 Ω, and R_(ref) should beapproximately the square root of (300Ω·3200Ω)=980Ω. To measure anunknown resistance in the range of 100 k-300 k ohms (as in, for example,a column of blood extending from one electrode to another via anarterio-venous fistula), the reference resistor R_(ref) 4 can be changedto approximately 200 k ohms and the filter capacitor R_(F) of low passfilter 9 at the input to the buffering amplifier 10 can be removedcompletely.

Because a voltage divider's output is a nonlinear function of itsresistance ratio, errors or noise in readings from the ADC 11 producetheir lowest fractional error (sensitivity) in the resultant calculationof R_(y) when it is equal to R_(ref), and the sensitivity increases themore R_(y) diverges from the reference resistance R_(ref). Specifically,it can be shown that the sensitivity in resistance ratio is as follows:

S _(ρ)=(1/ρ)·δ ρ/δΔα=2/[(1+Δα)(1−Δα)]=2/[1−(Δα)²]

When R_(y)=R_(ref), ρ=1, Δα=0 and S_(ρ)=2. Thus, for a change in Δα of0.001 (0.1% of the ADC full-scale) around this point, the calculatedresistance R_(y) changes by 0.002 or 0.2%. The sensitivity increases asρ diverges from 1, as shown in Table 1.

TABLE 1 ρ Δα S_(ρ) 1 0 2 2, 0.5 ±0.333 2.25 4, 0.25 ±0.6 3.13 5.83,0.172 ±0.707 4 10, 0.1 ±0.818 6.05 20, 0.05 ±0.905 11.03FIG. 3 shows that the noise/error sensitivity doubles at about a 6:1ratio of unknown/reference resistance, and triples at a 10:1 ratio.Resistance measurements outside this range may suffer in their increasedsensitivity to noise and error.

For calibration purposes, a switch SW₁ 12 can be used to make resistancemeasurements to calibrate out a point at R_(x)=0. Preferably this switch12 should be placed across the terminals V_(TA) and V_(TB) 3, or asclose to the terminals as feasible, which would give a true zero-pointcalibration. In practice, however, locating the switch 12 close to theterminals V_(TA) and V_(TB) 3 may make the switch 12 prone to externalnoise and surge voltages, and may introduce DC leakage current into thesubject media 1.

The series capacitances C1 and C2 6, and the use of square waves areimportant for unknown resistances that include an electrolyticconductive path. There are at least two reasons for this. First, it maybe important in many applications to prevent DC current from flowingthrough an electrolyte solution or a bodily fluid having similarproperties; otherwise electroplating and/or electrolysis of electrodesat the terminals V_(TA) and V_(TB) 3 can occur. In this circuit, thecapacitors C1 and C2 6 block DC currents. Furthermore, because thecapacitors may allow very small currents to flow (microamps or less),using an alternating square wave voltage may help to limit the averagecurrent further.

Secondly, in the event that a small electrochemical DC voltage isinduced in the subject media 1 (for example, the electrodes in a fluidpath may oxidize over time at different rates), this DC voltage can beblocked by the capacitors C1 and C2 6. Because the method forcalculating resistance takes differential measurements, any residual DCvoltage may be canceled out through the process of calculating theunknown resistance Rx of subject media 1.

Vascular Disconnect Detector

With the appropriate modifications of a conductivity measurement circuitsuch as the one described above, it is possible to detect theconductivity and changes in the conductivity of blood. Morespecifically, it is possible to detect the change that occurs in theconductivity of a volume of blood when air enters the volume. Thissituation can occur, for example, when an intravascular access sitebecomes dislodged in an extracorporeal blood circuit.

The circuit shown in FIG. 1 can be used to measure the resistance of avolume of fluid in a conductivity cell or conduit 1. For measurements ofR_(x) of a conductivity cell 1 representing the resistance orconductivity of a volume of dialysate solution, a convenient value forthe reference resistor R_(Ref) 4 can be chosen to be approximately 680ohms. For measurements of R_(x) of a conduit 1 representing theresistance or conductivity of a column of blood extending from a firstcannula or needle, through an arterio-venous fistula, to a secondcannula or needle, a convenient value for the reference resistor R_(Ref)4 can be chosen to be approximately 200 k ohms.

The advantages of using this circuit to monitor the continuity of acolumn of a bodily fluid such as blood or plasma include the following:

-   Capacitive coupling to the conductivity cell or conduit 1 blocks DC    current which could cause plating and corrosion of electrodes at    terminals VTA and VTB;-   Voltages and current levels are very low and decoupled for patient    safety;-   Current only flows briefly while the measurement is being taken. No    current flows between measurements.

With the lower reference resistor R_(Ref) 4 value (e.g. 680 ohms), thiscircuit is appropriately configured for dialysate conductivitymeasurements. With a much higher reference resistor R_(ref) 4 value(e.g. 200 k ohms) this circuit is appropriately configured for measuringthe resistance between an arterial needle and a venous needle to detectvascular needle dislodgement from an arterio-venous fistula.

Electrode Placement

The continuity of a fluid column leading from a fluid delivery apparatusto a patient's blood vessel or vascular graft can be monitored using theelectronic circuit described above. The fluid being delivered mayinclude blood or any electrolyte solution, including dialysate fluid.Although the following discussion will involve a hemodialysis system,the same principles of operation of the invention can apply to anydevice that is configured to deliver a fluid to a patient via a vascularaccess. In an embodiment illustrated by FIG. 4, the conductivity of avolume of blood or other fluid within a fluid flow circuit 100 of ahemodialysis machine 200 can be monitored electronically, usingelectrodes on each end of the volume that make direct contact with theblood or other fluid. Using an electrical circuit such as the one shownin FIG. 1, one electrode can be connected to the V_(TA) terminal, andthe other electrode can be connected to the V_(TB) terminal of thecircuit. The voltages applied to the electrodes by the circuit can besufficiently small (e.g., about 4 volts or less), sufficiently brief,and with DC voltages sufficiently decoupled so as to prevent any harm tothe patient. In this example, a fluid flow circuit 100 is shown,including an arterial access needle 102, an arterial catheter tubing104, an arterial catheter tubing connector 106, arterial blood circuittubing 108, a transition 110 between the blood circuit tubing 108 andhemodialysis machine 200, a blood pump inlet line 112, a blood pump 114,a blood pump outlet line 116, a dialyzer 118, a dialyzer outlet line120, air trap 122, a transition 124 between hemodialysis machine 200 andvenous blood circuit tubing 126, a venous catheter tubing connector 128,a venous catheter tubing 130, a venous access needle 132, and theintraluminal volume of that portion of the patient's blood vessel orfistula 134 that lies between the arterial access needle 102, and thevenous access needle 132. It should be noted that the inventiondescribed herein also encompasses circumstances in which the arterialaccess needle may reside in one blood vessel of a patient, while thevenous access needle may reside in a separate blood vessel some distanceaway from the arterial access site. Furthermore, the circuit describedabove may be used to monitor the integrity of a vascular access in afluid delivery system that does not have the venous return line shown inFIG. 4. In that case, for example, an electrode at location B could bepaired with an electrode in contact with fluid in a dead-end linecommunicating with a second needle or cannula accessing the blood vesselor vascular graft. In another example, an indwelling hollow cannula orsolid trocar in the vascular segment can be equipped with a conductivewire which could then serve as the second electrode in the monitoringsystem. The vascular segment being accessed may be a surgicallyconstructed arterio-venous fistula, and may also include an artificialconduit such as a Gortex vascular graft. The term ‘arterial’ is usedherein to denote the portion of the blood flow circuit that conductsblood away from the patient and toward the hemodialysis machine 200. Theterm ‘venous’ is used to denote the portion of the blood flow circuitthat conducts blood away from the hemodialysis machine 200 and backtoward the patient. The term ‘access needle’ is used to denote a needleor catheter device that penetrates the patient's vascular segment orfistula. In different embodiments it may be permanently fused orreversibly connected to a corresponding catheter tubing 104, 130.

The continuity of any segment of the fluid flow circuit 100 can bemonitored by positioning two electrodes in contact with the fluid oneither side of the fluid and blood-containing segment of interest. Inorder to monitor for a disconnection of the arterial access needle 102,or the arterial catheter tubing 104, or the venous access needle 132 orvenous catheter tubing 130, one electrode can be placed in continuitywith the lumen of the venous side of the blood flow circuit, while asecond electrode is placed in continuity with the lumen of the arterialside of the blood flow circuit. In one embodiment, the two electrodescan be positioned on or near the dialysis machine 200, with an electrodein contact with blood upstream of blood pump 110, and a second electrodein contact with blood downstream of the dialyzer 118 and/or air trap122. For example, the electrodes can be incorporated into transitionlocations 110 and 124.

In another embodiment, one of the electrodes can be positioned to be incontact with the fluid in the fluid flow circuit 100 at a point that iscloser to the vascular access site 134 than it is to the equipment (e.g.a dialysis machine) used to deliver fluid flow to the accessed bloodvessel or vascular graft. In a preferred embodiment, both electrodes canbe positioned to be nearer to the patient's blood vessel or vasculargraft than the equipment associated with the dialysis machine 200. Thismay further reduce electrical interference associated with the dialysismachine 200. An electrode A can be conveniently placed at or near thearterial catheter tubing connector 106 and a second electrode B can beconveniently placed at or near the venous catheter tubing connector 128.In this arrangement, the electrical continuity pathway from the firstelectrode through the patient's vascular access to the second electrodeis much shorter—and the electrical resistance lower—than the pathwayextending back toward the dialysis machine 200. In some cases, theaccess catheters 104 and 130 can be as short as about a foot, whereasthe arterial and venous tubings 108 and 126 can be about six feet long.Because of the electrical conductive properties of the fluid in thecircuit, the electrical resistance associated with the pathwayincorporating tubing 108 and 126, and components of the dialysis machine200, can be many times greater than the electrical resistance associatedwith the pathway through the patient's blood vessel or fistula 134.

Electrical interference associated with the dialysis machine 200 is thusreduced, and a change in electrical resistance due to an access-relateddisconnection can more easily be detected. Preferably, the electrodes Aand B are positioned to be more than 50% of the distance from thedialysis machine to the patient. More preferably (and moreconveniently), the electrodes A and B are located near the lastdisengageable fluid connection before reaching the patient. In oneembodiment of a hemodialysis system, the blood tubing 108 and 126 isapproximately 6 feet in length, and the arterial and venous cathetertubes 104, 130 are about two feet or less in length. A convenientlocation for electrodes A and B would then be at the arterial line andvenous line connectors 106, 128 (which can be, e.g. Luer type connectorsor modifications thereof) that connect the arterial and venous bloodcircuit tubes 108, 126 with the arterial and venous catheter tubes 104,130.

Connector Electrodes

As shown in FIGS. 5A and 5B, in one embodiment, a blood line connectorfor the blood circuit of a hemodialysis system may incorporateelectrodes that can make contact with any liquid within the lumen of theconnector. In one aspect, the electrode can comprise an annularconductive cap 310 placed at the tube-connection or proximal end 302 ofany suitable connector, such as, for example connector 300. Theelectrode is preferably constructed from a durable and non-corrosivematerial, such as, for example, stainless steel. The distal coupling end304 of connector 300 can be constructed to make a sealing engagementwith a corresponding Luer-type connector of an arterial or venouscatheter, for example. The inner annular surface 312 of the cap 310—inpart or in whole—can make contact with any liquid present within thelumen 314 of the connector. As shown in FIG. 5B, an O-ring 316 or asuitable sealant can be placed between the cap electrode 310 and theproximal end 302 of the connector to maintain a fluid-tight connectionbetween the connector and any flexible tubing attached to the connector.

An elastomeric O-ring may be particularly useful in hemodialysis orother extracorporeal systems in which the blood-carrying components aresubjected to disinfection or sterilization using heated liquids. Thethermal coefficients of expansion of the plastic components of aconnector may be sufficiently different from that of an incorporatedmetal electrode that a permanent seal may not be preserved after one ormore sterilization or disinfection procedures. Adding an elastomericcomponent such as an O-ring at the junction between an electrode and theconnector seat on which it is positioned may preserve the seal byaccommodating the different rates of expansion and contraction betweenthe electrode and the connector.

As shown in FIG. 6, in one embodiment, a conductive electrode 310(constructed of, e.g., stainless steel) can be incorporated into aportion of a connector 300 (either at its proximal end 302, oralternatively at its distal connecting end 304), over which the end of aflexible tubing 318 can be placed. In this embodiment, the electrode 310is generally cylindrical, and has a taper 320 on a proximal end topermit an easier slip-fit attachment of the end of a segment of flexibletubing 318 over the outside surface of the electrode 310. As shown inFIG. 6, the internal surface of the electrode 310 has an internal ledge322 that allows the electrode cap 310 to slip over and abut a proximalend 302 of connector 300. Connector 300 can be constructed of anysuitable hard material, including metal or more typically a plasticmaterial. The ledge 322 helps to ensure that a smaller diameter innersurface 312 of electrode 310 is properly positioned to make contact withany liquid (e.g. blood) that passes through the lumen 314 of connector300. The connections between connector 300 and electrode 310, andelectrode 310 and the termination of an overlying flexible tubing 318can be made air tight or permanent with any suitable adhesive compatiblewith the compositions of the components.

To ensure a more secure seal to prevent blood leakage between theconnector and electrode, and to limit the area under the electrode whereblood elements may migrate and become lodged, an O-ring 316 can beincorporated into the inner surface of electrode 310 near the electrodeinternal ledge 320. This is seen in enlarged detail in FIG. 6. In thisexample, the O-ring 316 seals between the stainless steel electrode 310and the distal end 302 of connector 300. A barb element 324 on theproximal end 302 of connector 300 can be incorporated in the connectordesign in order to hold the stretched end of the flexible tubing 318onto the proximal end 302 of connector 300. In an embodiment, theelectrode 310 is held in place by the portion of the flexible tube thatis stretched over both the electrode 310 and the barb 324 of connector300.

A wire 326 can be soldered, welded or otherwise secured onto the outersurface of electrode 310, and can travel under the overlying stretchedtubing 318 until exiting more distally along the connector 300. The wirecan thus conduct electrical signals to and from the electrode 310 as theinternal surface 312 makes contact with the intraluminal fluid (e.g.blood). In the example shown, wire 326 is soldered to a distal portionof electrode 310 and travels under tubing 318, to emerge at the abutmentof tubing 318 with a corresponding stop 326 of connector 300.

In another embodiment as shown in FIGS. 7A-7C, a connector 400 asdescribed in U.S. Patent Application Publication No. 2010/0056975 (thecontents of which are hereby incorporated by reference) has beenmodified so that a mid-portion 406 of the connector 400 can incorporatean electrode. Placement of the electrode along the mid-portion 406 ofthe connector 400 avoids having to alter the distal coupling end 404 ofthe connector, and avoids any alteration of the interaction between thetermination of the flexible tubing and the proximal end 402 of theconnector. In this example, the blood line connector 400 is constructedto make two different types of sealing connections on its distalcoupling end 404, including an internal screw-type connection 405 for aLuer-type connector of a patient access line, and an external press-intype connection 407 with a dialysis machine port for recirculation ofpriming and disinfecting fluid through the blood carrying components ofa dialysis system. The press-in feature 407 is formed having afrustoconical shape on the outside surface of the distal end 404 of theconnector 400, while the Luer-compatible screw-type feature 405 isformed on the corresponding internal surface of the distal end 404 ofthe connector 400. The outside surface of the frustoconical member isconstructed to make sealing engagement with the seat of a matingconnector of a dialysis machine 200 or other device. A pair of lockingarms 408 extending proximally from the distal coupling end 404 of theconnector 400 can each have a barbed portion 409 to engage acorresponding locking feature on a mating connector on the dialysismachine, and a finger depression portion 410 to aid in disengaging thebarbed portions 409 from the dialysis machine. The barbed portion 409helps to lock the frustoconical member in sealing engagement with itsmating connector on the dialysis machine when making a press-in type ofconnection. The distal ends of the locking arms can be constructed toattach to the connector via a flange 411 located proximal to thefrustoconical portion 407 of the connector 400. The connector 400 has aproximal tubing attachment end 402 to sealingly engage a flexible tube.The tubing attachment end 402 may have one or more barb features 412 tohelp prevent disengagement of the end of a flexible tube from theconnector 400.

FIG. 7B shows a side view of connector 400, bringing into view an accessfeature or port 420 that can permit placement of an electrode in directcommunication with the lumen of connector 400. In other embodiments, theaccess feature may house an elastomeric stopper—with or without aseptum—to permit sampling of fluid from within the lumen 414 ofconnector 400 using a syringe with a sharp or blunt needle.Alternatively, the feature may serve as a port to allow connection ofanother fluid line to the lumen 414 of connector 400.

In yet another embodiment, the mid-portion 406 of connector 400 may havetwo access ports, as shown in the cross-sectional view of FIG. 7C. Afluid access port 420 a can serve as a sampling port, and an electrodeport 420 b can serve as an electrode cradle. An elastomeric stopper 422within sampling port 420 a can be shaped to extend to the lumen 414 ofconnector 400, simultaneously permitting sampling of fluid in the lumen414 with a needle, while maintaining an air-tight seal. Alternatively, aLuer-type connector having a septated cap or seal can be incorporatedinto the port, which is capable of connecting with a syringe or catheterhaving a mating Luer-type connector. An electrode port 420 b can serveas a seat or cradle for an electrode 424. In can be press-fit orcemented into position, and sealed with an adhesive, or with an O-ring416 as shown. A wire 426 can be soldered, welded or otherwise securedonto the outer surface of electrode 424, and can travel proximallytoward dialysis machine 200 with the arterial tubing 108 or venoustubing 126 to which connector 400 is attached.

In any of the above electrode embodiments, the electrodes may bereplaced by a suitably sized thermistor, or combination of a thermistorand electrical conductor, for the additional purpose of monitoring thetemperature of the fluid passing through connector 300, 400 or variantsthereof.

Wire Assembly

In one embodiment, the wires carrying electrical signals to or from apair of electrodes on connectors 106, 128 (one on the arterial side andone on the venous side of the blood flow circuit) can travel separateand apart from the blood tubing 108, 126 back toward dialysis machine200, where they ultimately terminate and connect to, a conductivitydetecting circuit, such as the conductivity circuit shown in FIG. 1. Theconductivity circuit, in turn, provides an appropriately configuredsignal to a processor on the dialysis machine to determine whether achange in fluid conductivity consistent with an access disconnection hasoccurred. If so, the processor can trigger an alarm condition, or caninitiate a shut-down of blood pump 114, and trigger a mechanicalocclusion of blood tubing 108 and/or 126, for example.

Wires that extend together or separately between the dialysis machineand the patient are at risk of getting tangled, broken or becomingdisconnected. Therefore, preferably, each wire 326 or 426 can beattached, fused, or otherwise incorporated into its associated tubing108, 128. Incorporating a wire into its associated tubing provides aconvenient way of protecting the wires and connections, and simplifyingthe interface between the patient and the dialysis apparatus. Exemplarymethods of achieving this are shown in FIGS. 8A-8D. In a preferredembodiment, the tubing is comprised of a flexible material (e.g.,silicone) that can be formed in an extrusion process. As shown in FIG.8A, a loose wire mesh may be embedded in the flexible silicone tubing asit is formed and extruded, similar to fiber reinforcement of flexibletubing. As shown in FIG. 5A, a wire mesh 500 can be embedded within thewall of the flexible tubing 502 during extrusion, in a manner similar tothe construction of a fiber-reinforced tube. As shown in FIG. 8B, aninsulated wire 504 can be joined to the external surface of its adjacenttubing 506, either during a secondary extrusion process, or a process inwhich the two structures are joined by an adhesive, for example. Asshown in FIG. 8C, a second extrusion producing a secondary concentriclayer of tubing material 508 can be made to capture a wire running alongthe external surface of the tubing after the primary extrusion. As shownin FIG. 8D, the tubing 510 during formation can also be co-extruded witha wire 512 embedded in the wall of the tubing.

In some of the above methods, the resulting tube-wire combination mayhave a tendency to curl because of the difference in thermalcoefficients of expansion between the wire and the silicone material ofthe tubing. As the material cools after extrusion, the silicone maycapture the embedded wire tightly, causing the cooled tube-wire bundleto curl. In a preferred embodiment, the wire lumen of the extrusion dieis constructed to be large enough to accommodate a cross-sectional areasignificantly larger than the cross-sectional area of the wire to beembedded. Then as the silicone cools, the passageway surrounding thewire does not shrink to the point of tightly encasing the wire. Aco-extrusion process incorporating an insulated wire can generate atube-wire bundle as shown in FIG. 9. In this example, flexible tubing514 is a co-extrusion of a fluid-carrying lumen 516 and a wire-carryinglumen 518. Preferably, the wire 520 is multi-stranded for flexibilityand durability, and is coated or sheathed in a durable, flexiblesynthetic insulating material 522, such as, for example, PTFE. APTFE-based sheath 522 of the stranded wire 520 can sustain the hightemperatures associated with the silicone tubing extrusion process, sothat its integrity is maintained along the section 524 of the wire thatultimately exits the tubing for connection either to the dialysismachine 200 or the patient line connectors 106, 128. A coating orsheathing may also help prevent the wire from adhering to the side wallsof the wire-carrying lumen after extrusion and during cooling.

FIG. 10 shows a cross-sectional view of an exemplaryconnector-wire-tubing assembly. The proximal tubing connection end of aconnector 400 is shown with the end of a double-lumen tubing 514attached. The fluid-carrying lumen 516 is press-fit and/or cemented tothe proximal end of connector 400, allowing for fluid flow through thecentral lumen 414 of connector 400. Stranded wire 520 is soldered orotherwise attached to electrode 424, which is in conductive contact withany fluid present within the lumen 414 of connector 400. Thenon-connecting portion of the wire 520 that travels outside tubing 514is preferably sheathed in an insulating synthetic coating, such as, forexample, PTFE. Optionally, this portion of both the exposed and sheathedwire may also be sealed with a sealant, such as RTV. The sheathed wire522 enters the wire-carrying lumen 518 of tubing 514 near itstermination onto connector 400. The wire/tubing bundle then makes itsway toward the dialysis machine 200, where the wire emerges from thetubing to make a connection to a conductivity circuit such as the oneshown in FIG. 1.

FIG. 11 shows an exemplary extracorporeal circuit 210 that may be usedas a removable, replaceable unit in a hemodialysis apparatus 220 asshown in FIG. 12. In this embodiment, the extracorporeal circuitcomprises a blood pump cassette 114, dialyzer 118, venous return airtrap 122, arterial blood tubing 108, venous blood tubing 126, arterialcatheter connector 106, and venous catheter connector 128. The arterial106 and venous 128 connectors may be of a type similar to the connector300 shown in FIGS. 5A and 5B, or similar to the connector 400 shown inFIGS. 7A-7C, or variants thereof. The arterial 108 and venous 126 bloodtubes may be of a type shown in FIGS. 8A-8D, or FIG. 9. Wires formingterminal connections to electrodes on connectors 106 and 128 may exitarterial 106 and venous 126 tubes as segments 524A and 524B to make aconnection with a connector that ultimately passes the connectionthrough on the dialysis apparatus to terminals associated with aconductivity circuit such as that shown in FIG. 1. In the embodimentshown, the connector 526 is mounted to a support structure 212 for theblood pump 114 and air trap 122.

FIG. 12 shows an exemplary hemodialysis apparatus 220 that is configuredto receive the extracorporeal circuit 210 shown in FIG. 11. In thisillustration, the dialyzer 118 is already mounted onto the apparatus220. A base unit 220 receives the control ports of a mating blood pumpcassette 114. Sets of raceways or tracks 222 help to organize the pairof arterial 106 and venous 126 blood tubes when not extended out andconnected with a patient. A connector 224 receives and passes throughthe connections made between wire segments 524A and 524B and connector526 to the terminal connections of a conductivity circuit such as thatshown in FIG. 1. A tubing occluder 226 is positioned to receive venousblood tube 126 after it exits air trap 122, and arterial blood tube 108before it reaches blood pump cassette 114. The occluder 226 may beactuated pneumatically or electromechanically, for example, whenever analarm condition occurs that requires cessation of extracorporeal bloodflow. A set of arms of occluder 226 can be configured to rotate againstthe walls of the flexible tubes, constricting or stopping fluid flowwithin them. Thus, a controller installed within apparatus 220 canreceive a signal from a conductivity circuit similar to FIG. 1, thesignal representing the electrical resistance of the column of fluid orblood between the electrodes mounted on connectors 106 and 128. Becausethe connectors are positioned much closer fluidically to the patient'sblood vessel or fistula 134 than to the blood pump 114, dialyzer 118 andair trap 122, the signal associated with the fluid path through theblood vessel or fistula 134 can discriminate between an intact and aninterrupted column of blood or fluid between the connectors 106/128 andthe patient's blood vessel or fistula 134. The controller can beprogrammed to respond to an electrical resistance detected by theconductivity circuit found to exceed a pre-determined value. Dependingon the circumstances, the controller may then trigger an alarm to alertthe patient to a possible disconnection of blood flow, and may alsooptionally command the occluder 226 to cease extracorporeal flow to andfrom the patient.

Operation of the Disconnect Detection Circuit

FIG. 13 shows test results utilizing the disconnect detection circuitdescribed above and shown in FIG. 1. In this case, a hemodialysis bloodcircuit and apparatus was employed that is similar to that disclosed inU.S. Patent Application Publication Nos. 2009/01 14582 and 2010/0056975,(the contents of which are hereby incorporated by reference). Theextracorporeal circuit 210 shown in FIG. 11, comprises a blood pump 114,dialyzer 118, air trap 122, venous blood circuit tubing 126, andarterial blood circuit tubing 108. Extracorporeal circuit 210 mates to ahemodialysis apparatus 220 similar to the one shown in FIG. 12. Theblood flow circuit tested included a pair of membrane-based blood pumpsarranged on a blood pump cassette 114 shown in FIG. 11, a dialyzer 118,a venous return air trap 122, an arterial blood tubing set 108, a venousblood tubing set 126, arterial and venous connectors 106 and 128, andcatheter tubing sets 104, 130 connected to vascular access needles 102,132 as shown in FIG. 4. The needles 102, 132 were placed in a containerholding anticoagulated bovine blood. The blood tubing set 108 and 126was approximately six feet long, and the catheter tubing sets 104 and130 were approximately two feet long or less. The needles werealternately manually placed in or withdrawn from the container duringblood flow to simulate disconnection of a needle from a fistula or bloodvessel. Periods A, C and F in FIG. 13 represent the times during whichthe needles were submerged in the blood in the container. The electricalresistance measured by the disconnect detection circuit shown in FIG. 1during these periods averaged between 120,000 and 130,000 ohms. PeriodsB and E in FIG. 13 represent the times during which the venous returnneedle 132 (under positive pressure from the blood pumps) was withdrawnseveral centimeters above the surface of the blood within the container,forming a stream of blood mixed with air as the blood exited the venousreturn needle and entered the container of blood below. The electricalresistance measured during these periods averaged between 140,000 and150,000 ohms. Period D represents the time during which one of theneedles was completely removed from the container, creating a fully openelectrical circuit. The electrical resistance measured during thisperiod averaged between about 160,000 and 180,000 ohms. Thus acontroller can be readily programmed to distinguish the difference inthe monitored resistance of the electrical circuit between anuninterrupted and an interrupted flow of blood. These results showedthat an interruption of the continuity of the blood between the arterial102 and venous 132 needles can reliably produce a detectible change inthe measured electrical resistance between two electrodes when placedrelatively closer to the arterial and venous access sites than to theblood processing components 114, 118 and 122 of the extracorporeal bloodcircuit. Furthermore, even a partial interruption of the continuity ofblood flow (as in the streaming of blood through air) can be reliablydetected, albeit with a smaller change in the measured electricalresistance.

1. A system for detecting the disconnection of a vascular access devicefrom a blood vessel or vascular graft, comprising: a fluid deliverydevice for providing fluid through a first conduit into a first site ofthe blood vessel or graft; a first electrode in contact with the lumenof the first conduit; a second electrode in fluid communication with asecond site of the blood vessel or graft; an electronic circuitconnected to the first and second electrodes, and configured to delivera control signal to the first and second electrodes in order to measurethe electrical resistance of a fluid between the first and secondelectrodes, wherein at least one of the electrodes is located closer tothe blood vessel or graft than to the fluid delivery device.
 2. Thesystem of claim 1, wherein the fluid delivery device comprises a pump.3. The system of claim 1, wherein the fluid delivery device comprises ahemodialysis blood flow circuit.
 4. The system of claim 1, wherein thesecond electrode is in contact with the lumen of a second conduitaccessing the blood vessel or graft at the second site.
 5. The system ofclaim 4, wherein the second conduit comprises part of a fluid flow pathfrom the blood vessel or graft to the fluid delivery device.
 6. Thesystem of claim 5, wherein the first conduit comprises a first connectorconnecting a first vascular access catheter to a first tube segment, thesecond conduit comprises a second connector connecting a second vascularaccess catheter to a second tube segment, and the first and secondvascular access catheters are shorter than the first and second tubesegments.
 7. The system of claim 6, wherein the first connector includesthe first electrode and the second connector includes the secondelectrode.
 8. The system of claim 1, wherein the first conduit comprisesa double lumen flexible tube having a first lumen for carrying thefluid, and a second lumen for carrying a wire connecting the firstelectrode to the electronic circuit.
 9. The system of claim 1, furthercomprising a controller configured to receive a signal from theelectronic circuit, the signal representing the electrical resistancebetween the electrodes, wherein the controller is programmed to triggeran alert signal when the electrical resistance value exceeds apre-determined threshold.
 10. The system of claim 9, wherein the alertsignal comprises an electrical command to a tubing occluder apparatus,wherein the tubing occluder apparatus includes a mechanical occluderarranged and configured to occlude the conduit.
 11. An apparatus formonitoring the continuity between a vascular access device and a bloodvessel or vascular graft segment, comprising: a first and secondvascular connector, the first connector being attached on a proximal endto a distal end of a fluid-carrying lumen of a first double-lumen tube,and the second connector being attached on a proximal end to a distalend of a fluid-carrying lumen of a second double-lumen tube, the firstconnector comprising a first electrode in contact with a lumen of thefirst connector and electrically connected to a wire within awire-carrying lumen of the first double-lumen tube, and the secondconnector comprising a second electrode in contact with a lumen of thesecond connector and electrically connected to a wire within awire-carrying lumen of the second double-lumen tube, wherein, the wirewithin the first double-lumen tube and the wire within the seconddouble-lumen tube are each connected to an electrical connector at aproximal end of the double-lumen tubes.
 12. The apparatus of claim 11,wherein a distal end of each connector comprises a locking member forproviding a reversible, air-tight connection between the connector and amating connector of a vascular catheter.
 13. The apparatus of claim 12,wherein a proximal end of the fluid-carrying lumen of the firstdouble-lumen tube is connected to a blood pump, and a proximal end ofthe fluid-carrying lumen of the second double-lumen tube is connected toan air trap.
 14. The apparatus of claim 13, wherein the air trap and theblood pump are configured for reversible connection to a dialyzercartridge.
 15. A vascular connector comprising a proximal fluidconnection end, a distal fluid connection end, and an electrodeconfigured to electrically connect a fluid-carrying lumen of theconnector with a wire external to the vascular connector.
 16. Thevascular connector of claim 15, wherein the proximal fluid connectionend is configured to fluidly connect with an end of a flexible tube, andthe distal fluid connection end is configured to reversibly connect witha mating connector of a vascular catheter.
 17. The vascular connector ofclaim 15, wherein the electrode is installed in a conduit on theelectrode connecting the lumen of the connector with an external surfaceof the connector.
 18. The vascular connector of claim 17, wherein theelectrode is lodged within the conduit, forming an air-tight sealbetween the lumen and the external surface of the connector.
 19. Thevascular connector of claim 18, wherein an elastomeric member isinstalled between the electrode and the conduit, contributing to theair-tight seal between the lumen and the external surface of theconnector.
 20. An electrical circuit for measuring the resistance of aliquid between a first and second electrode, the first electrodeconnected to a first terminal of the electrical circuit, and the secondelectrode connected to a second terminal of the electrical circuit,comprising: a capacitor C1 connected on a first end to the firstterminal and a capacitor C2 connected on a first end to the secondterminal; a known reference resistance Rref connected on a first end toa second end of capacitor C1; switching means for connecting either; a)a first reference voltage V+ to a second end of Rref, and a lower secondreference voltage V− to a second end of C2 to form a first switchconfiguration or; b) the first reference voltage V+ to the second end ofC2 and the lower second reference voltage V− to the second end of Rrefto form a second switch configuration; and measuring means for measuringa voltage Vsense at the connection between C1 and Rref; wherein theelectrical circuit is configured to determine the value of theresistance of the liquid based on the known reference resistance Rrefand the observed voltage Vsense for each of the first and second switchconfigurations.
 21. The electrical circuit of claim 20, wherein theresistance-Rref is chosen to permit conductivity measurement of anelectrolyte solution suitable for intravascular infusion.
 22. Theelectrical circuit of claim 21, wherein the electrolyte solutioncomprises dialysate solution.
 23. The electrical circuit of claim 20,wherein the resistance Rref is chosen to permit measurement of theresistance of a volume of blood between the first and second electrodes.